期刊
JOURNAL OF LIPID RESEARCH
卷 60, 期 7, 页码 1293-1310出版社
ELSEVIER
DOI: 10.1194/jlr.M093534
关键词
antioxidants; lipids; chemistry; lipids; peroxidation; mass spectrometry; mitochondria; Saccharomyces cerevisiae; ubiquinone; steroidogenic acute regulatory protein-related lipid transfer
资金
- National Science Foundation [MCB-1330803]
- National Institutes of Health [T32 GM 008496]
- U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research
- Quantitative and Computational Biosciences Collaboratory Postdoctoral Fellowship
Coenzyme Q (CoQ or ubiquinone) serves as an essential redox-active lipid in respiratory electron and proton transport during cellular energy metabolism. CoQ also functions as a membrane-localized antioxidant protecting cells against lipid peroxidation. CoQ deficiency is associated with multiple human diseases; CoQ(10) supplementation in particular has noted cardioprotective benefits. In Saccharomyces cerevisiae, Coq10, a putative START domain protein, is believed to chaperone CoQ to sites where it functions. Yeast coq10 deletion mutants (coq10 Delta) synthesize CoQ inefficiently during log phase growth and are respiratory defective and sensitive to oxidative stress. Humans have two orthologs of yeast COQ10, COQ10A and COQ10B. Here, we tested the human co-orthologs for their ability to rescue the yeast mutant. We showed that expression of either human ortholog, COQ10A or COQ10B, rescues yeast coq10 Delta mutant phenotypes, restoring the function of respiratory-dependent growth on a nonfermentable carbon source and sensitivity to oxidative stress induced by treatment with PUFAs. These effects indicate a strong functional conservation of Coq10 across different organisms. However, neither COQ10A nor COQ10B restored CoQ biosynthesis when expressed in the yeast coq10 Delta mutant. The involvement of yeast Coq10 in CoQ biosynthesis may rely on its interactions with another protein, possibly Coq11, which is not found in humans. Coexpression analyses of yeast COQ10 and human COQ10A and COQ10B provide additional insights to functions of these START domain proteins and their potential roles in other biologic pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据